LDL Receptor-related Protein (LRP1) is an endocytic receptor for as many as 100 distinct ligands including multiple proteases. In many cells, including neurons and Schwann cells, ligand-binding to LRP1 activates cell-signaling factors such as Src, ERK/MAP kinase, and Akt. LRP1 also regulates the plasma membrane abundance of other membrane proteins, including uPAR and tumor necrosis factor receptor-I (TNFRI). In macrophages and microglia, LRP1 regulates expression of cytokines and microRNA-155. As a result, the membrane-anchored form of LRP1 is potently anti-inflammatory. However, LRP1 may be shed from the cell surface, generating a soluble species that is potently pro-inflammatory. The balance between membrane-anchored and shed LRP1 appears to regulate important processes such as neuro-inflammation, central sensitization in the spinal cord, and chronic neuropathic pain. Understanding biochemical pathways that control this balance is a major goal for this laboratory. The image on this page shows cultured microglia, which have been transformed into an activated state by LRP1 ligand.